Interpretive Summary: Bovine viral diarrhea virus (BVDV) causes significant losses to U.S. cattle producers. Two types of BVDV exist in the U.S., BVDV genotype 1 (BVDV1) and BVDV genotype 2 (BVDV2). This paper reviews the differences between BVDV1 and BVDV2 and details how those differences have impacted on BVDV control programs. Vaccination is one of the key elements of BVDV control programs. This review addresses changes in vaccines that were made in response to the recognition of differences between BVDV1 and BVDV2.

Technical Abstract:
In the early 1990's research groups in North America noted that a newly recognized severe acute form of bovine viral diarrhea virus infection, referred to as hemorrhagic syndrome or severe acute BVDV (SA BVDV), was associated with a genetically distinct subgroup of BVDV strains. This new subgroup was named BVDV genotype 2 or BVDV2. All BVDV strains previously characterized in the literature belonged to a separate genotype, BVDV1. However, not all strains identified as BVDV2 were associated with severe acute infections. One of the earliest studies, which characterized BVDV2 strains, found that 11 out of 76 BVDV2 strains were isolated from persistently infected animals born to dams previously vaccinated against BVDV. Characterization of BVDV strains used in the vaccines revealed that the vaccine strains belonged to the BVDV type 1 genotype. Subsequent surveys of BVDV strains isolated from clinical submissions to diagnostic laboratories and contaminated fetal calf serum suggested that the ratio of BVDV2 to BVDV1 strains in the U.S. approached 50%. Further, while antigenic cross reactivity is seen between BVDV1 and BVDV2 strains, a log or more difference is typically observed in titers against viruses from different genotypes. These observations prompted vaccine manufacturers in North America to produce vaccines against BVDV that contained antigens from both BVDV1 and BVDV2 strains. Under experimental conditions these new vaccines offered improved protection against type 2 strains, however field data is still insufficient to assess their efficacy in practice.
Recently questions have been raised regarding the possibility of recombination between cytopathic BVDV vaccines strains, contained in the same modified live vaccine, resulting in the generation of a new noncytopathic strain. To date, there have been no observations, either in vitro or in vivo, of recombinations between cytopathic viruses giving rise to noncytopathic viruses. In addition there have been no reports of increased reproductive disease within herds under vaccine programs using combination type 1 and type 2 vaccines.
In addition to genotypes, BVDV strains may also be segregated into subgenotypes. Two subgenotypes of both BVDV1 (BVDV1a and BVDV1b) and BVDV2 (BVDV2a and BVDV2b) have been reported in North American. BVDV2a predominates with BVDV2b isolation a rare event. In contrast, BVDV1a and BVDV1b are both commonly isolated. Antigenic differences observed between strains from the BVDV1a and BVDV1b subgenotypes have led to the suggestion that protection may be improved by inclusion of strains from both BVDV1a and BVDV1b in vaccines in addition to BVDV2. The cost to benefit ratio of this proposal is currently a matter of debate.